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Alzheimer's disease (AD) is a common age-related degenerative disease. Galantamine hydrobromide (GAH) is an acetylcholine inhibitor that can alleviate memory impairment caused by AD. In this investigation, we developed a novel microcapsule (Hydrogel-GAH) comprising sodium carboxymethylcellulose and mesoporous silica nanocarriers as the core material and sodium alginate and polydopamine as the shell-encapsulating GAH. These microcapsules are designed for gradually slowing the release of GAH in the small intestine, facilitating targeted drug delivery, reducing the frequency of patient dosing, improving the efficiency of drug administration, and improving patient compliance. These findings suggest that hydrogel microcapsules provides an ideal drug delivery bridge for AD treatment via oral administration. [Display omitted] • Hydrogel-GAH microparticles could sustainably release GAH in the intestine and mitigate its gastric side effects. • Hydrogel-GAH microparticles showed reduced dosing frequency, significant therapeutic efficacy, and desirable biosafety. • Hydrogel-GAH microparticles were promising drug delivery systems, showing the potential value for clinical translation. Alzheimer's disease (AD) is a progressive neurodegenerative disease and is the most common type of dementia in aged individuals. Galantamine hydrobromide (GAH) is an approved medication for AD that has been shown to significantly enhance cognitive function, effectively manage behavioral symptoms, and improve performance in essential daily activities. However, the side effects of these drugs include nausea and vomiting, significant fluctuations in blood concentration, and poor patient compliance. Therefore, improving the route of administration and enhancing therapeutic efficacy are major research focuses. Here, we propose the use of hierarchically structured hydrogel-encapsulated mesoporous silica nanocarriers (MSNs) to encapsulate GAH, with the goal of minimizing adverse reactions in the stomach. By enabling the slow release of the drug over an extended period, these hydrogels aim to reduce the frequency of dosing, thereby improving the efficiency of drug administration and enhancing patient compliance. Owing to these properties, drug-carrying microcapsules are capable of achieving optimal drug delivery and have emerged as excellent candidates for AD therapy. We believe that this technology has the potential to significantly impact clinical treatment. [ABSTRACT FROM AUTHOR]

Schematic illustrations of KLVFF@LIP-CeO 2 for the treatment of AD. (a) Preparation of KLVFF@LIP-CeO 2 by a thin-film hydration and extrusion method. (b) KLVFF@LIP-CeO 2 is intranasally delivered to APP/PS1 mice. KLVFF can inhibit Aβ aggregation via hydrogen-bonding interactions, whilst CeO 2 can scavenge multi-ROS via facile redox switching between Ce4+ and Ce3+. This system can simultaneously alleviate Aβ deposition and oxidative stress in APP/PS1 mice, corporately resulting in the neuroprotective effects and the rescue of cognitive impairment. [Display omitted] • KLVFF@LIP-CeO 2 enabled co-delivery of Aβ-degrading peptide and ROS-scavenging nanozyme for synergistic therapy of AD. • Intranasal administration enabled sufficient drug accumulation inbrain. • KLVFF@LIP-CeO 2 alleviated Aβ deposition and oxidative stress, contributing torscue of cognitive impairment of APP/PS1 mice. β-Amyloid (Aβ) aggregation and oxidative stress are primary pathological features of Alzheimer's disease (AD). Combination therapies that target brain tissue and corporately address these main pathological factors are required for effective AD treatment. Here, we developed a multifunctional liposome delivery system (KLVFF@LIP-CeO 2) for co-delivery of Aβ-targeted KLVFF and reactive oxygen species (ROS)-responsive Ceria (CeO 2) through intranasal administration. After Aβ 1-42 -induced ROS and apoptosis in HT22 cells, KLVFF@LIP-CeO 2 exhibited significant protective effects by inhibiting Aβ aggregation and scavenging multi-ROS. With these features, we verified the therapeutic effectiveness of KLVFF@LIP-CeO 2 in APPswe/PSEN1dE9 (APP/PS1) model mice. After intranasal administration, KLVFF@LIP-CeO 2 demonstrated sufficient and rapid accumulation in the brain and significantly alleviated Aβ deposition and oxidative stress, corporately contributing to the rescue of cognitive impairment of APP/PS1 mice. These results highlight the clinical potential of these multi-targeted nanoparticles for synergistic therapy of AD. [ABSTRACT FROM AUTHOR]